Maternal metabolic abnormalities in twin-to-twin transfusion syndrome at mid-pregnancy.

We report abnormal maternal laboratory parameters in twin-to-twin transfusion syndrome (TTTS) at mid-pregnancy. A retrospective chart review was undertaken of 109 patients with TTTS evaluated for placental laser surgery. Complete blood count (CBC), blood type and Rh factor, urine analysis and serum chemistry panel were obtained preoperatively, with the CBC and serum albumin repeated on the first postoperative day. The mean gestational age was 21.2+/-1.7 weeks. Initial abnormal values included hematocrit (32.1+/-3.0%), hemoglobin (11.0+/-1.03 g/dl), serum magnesium (1.71+/-0.17 mg/dl), total protein (6.08+/-0.55 g/dl) and albumin (3.06+/-0.34 g/dl). Despite minimal blood loss and conservative fluid replacement mean hematocrit, hemoglobin, and albumin were 27.3+/-2.74%, 9.3+/-0.94 g/dl and 2.56+/-0.23 g/dl, respectively on postoperative day one. Weight gain (8.0+/-5.5 lb.) and low urinary output were characteristic peri-operative events. Maternal hypoproteinemia and anemia occur in TTTS at mid-pregnancy. This may contribute independently to amniotic fluid production rates in the fetuses, and explain in part the maternal sensitivity to intravenous fluids in multiple pregnancy.

Duration of cytochrome P-450 2E1 (CYP2E1) inhibition and estimation of functional CYP2E1 enzyme half-life after single-dose disulfiram administration in humans.

Disulfiram (DSF) is a mechanism-based inhibitor of cytochrome P-450 2E1 (CYP2E1), resulting in loss of CYP2E1 protein and activity, which may be useful in preventing CYP2E1-mediated xenobiotic toxicity. The duration of inhibition after a single DSF dose is, however, unknown. The purpose of this investigation was to determine this duration, and CYP2E1 formation and degradation rates, in humans. Oral chlorzoxazone (CLZ) was used as the selective in vivo probe for CYP2E1. Healthy subjects received CLZ to determine baseline CYP2E1 activity (CLZ plasma clearance and 6-hydroxychlorzoxazone fractional metabolic clearance). One week later, DSF (500 mg orally) was administered at bedtime, and CLZ administered the following morning and 3, 6, 8, 10, and 13 days after DSF. A terminal DSF metabolite, 2-thiothiazolidine-4 carboxylic acid, was also measured in each 24-h urine sample. The mean CLZ clearance and 6-hydroxychlorzoxazone fractional metabolic clearance on the first day declined to 10.2 and 5.5% of baseline values, indicating rapid and profound CYP2E1 inhibition. CYP2E1 activity returned to half that of control on day 3, and to baseline values on day 8. Assuming zero-order synthesis and first-order degradation, the in vivo CYP2E1 synthesis rate and degradation half-life was estimated to be 11 +/- 5 nmol/h and 50 +/- 19 h, respectively. Significant amounts of 2-thiothiazolidine-4 carboxylic acid were present only on day 1, suggesting that the return of in vivo CYP2E1 activity was not caused by inhibitor washout, but by enzyme resynthesis. Results regarding CYP2E1 disposition may be useful for modeling the effects of CYP2E1 inducers and inhibitors. For prevention of CYP2E1-mediated bioactivation, depending on protoxicant disposition, a second DSF dose might be necessary to completely prevent toxicity.

Critical review of articles regarding pregnancy exposures in popular magazines.

To determine the scope of teratogen information available to the public through the media, a survey of 15 popular magazines was conducted. All 1985 issues of the selected magazines were reviewed for articles addressing pregnancy exposure concerns, yielding 56 articles from 10 magazines. The remaining 5 publications provided no pertinent articles. Two health professionals, both experienced teratology counselors, independently rated each article for accuracy of content and quality of presentation based on standardized evaluation criteria. The findings were compared and agreement for all criteria in each article was reached by the 2 reviewers. Regarding the quality of the information in the 56 articles, 31 (55.4%) were scored as misleading or inaccurate. On examination of overall presentation, 26 (46.4%) were rated as alarming and 8 (14.3%) presented a false sense of security; 22 (39.3%) provided a balanced presentation. A review of the types of articles rated revealed 19 (33.9%) general overviews of pregnancy issues, 18 (32.1%) news stories, 17 (30.4%) question-and-answer columns, and 2 (3.6%) feature stories. Of the reviewed papers, 7 (12.5%) included a citation from which the primary data could be obtained and only 14 of the articles (25%) suggested that the reader contact her/his healthcare provider regarding the issues. We conclude that the information available in popular magazines regarding exposures in pregnancy is frequently misleading, alarming, and unsupported by the scientific literature.

Unexpected accumulation of acyclovir in breast milk with estimation of infant exposure.

Although acyclovir is prescribed to women of reproductive age, no information currently exists regarding the advisability of its use in lactating women. This report documents the first known case of acyclovir transfer to an infant through breast milk. Maternal plasma, milk, and infant urine were collected following a 200-mg oral dose of acyclovir. The drug concentration in breast milk exceeded the corresponding plasma concentration except at the time of peak plasma concentration. This would not be expected on the basis of simple diffusion, and might be caused by a facilitated or active transport mechanism. Such a mechanism has not been described for any drug in human breast milk. Subtherapeutic amounts of acyclovir were documented in the infant, and we discuss the potential effects on neonatal immune function. The use of acyclovir in lactating women remains controversial until further study can clarify pertinent questions.

Twin transfusion syndrome: successful in utero treatment with digoxin.

A pregnancy complicated by twin transfusion syndrome is presented. When signs of cardiac failure (edema, ascites and hydramnios) persisted in the recipient twin, maternal digoxin therapy was instituted at 27 weeks' gestation. The signs of failure resolved, and the twins were delivered electively by cesarean section at 34 weeks. At birth, the syndrome was confirmed by examination of the infants and placenta. Both infants survived. Digoxin therapy is recommended for fetal heart failure from circulatory overload in twin transfusion.

Flurbiprofen in dysmenorrhea.

Reports on the efficacy of flurbiprofen for dysmenorrhea conflict. We gave 59 dysmenorrheic patients flurbiprofen (50 mg), aspirin (650 mg), or placebo. Paired drug comparisons showed that patients preferred flurbiprofen and that it was more effective in relief of pain, in allowing patients to pursue normal daily function, and in reducing the need for additional analgesics. Except in patient preference, aspirin was only marginally superior to placebo, There was an increase in minor side effects in the flurbiprofen group, but our results indicate therapeutic utility for flurbiprofen in dysmenorrhea.

Phenytoin metabolism in pregnancy.

Approximately 45% of patients with epilepsy experience an increase in seizure frequency during pregnancy. Despite the availability of effective anticonvulsant medications, there has been no decrease in reported seizure frequency accompanying pregnancy in the past 35 years. The authors prospectively studied concentrations of phenytoin (DPH) and its metabolites in 5 patients throughout pregnancy and during the postpartum period. The concentrations of phenytoin, as well as both unconjugated and conjugated forms of its principal metabolite, 5-(4-hydroxyphenyl)-5-phenylhydantoin (4-OH-DPH), were measured in plasma and urine by a precise high-pressure liquid chromatography method. Four patients experienced a decrease in plasma DPH during gestation, 3 of whom developed seizures at a time of low plasma DPH concentration. Within the therapeutic range, small increments in dosage resulted in large increments in plasma DPH levels, and in the postpartum period high levels of DPH were encountered if the dosage was not reduced. As pregnancy progressed, there was a decrease in the percentage of the daily dosage of DPH excreted as 4-OH-DPH. Based on these observations, the authors conclude that 1) pregnancy is associated with altered DPH absorption or metabolism or both, and 2) periodic measurement of plasma DPH concentration is valuable when managing a pregnant epileptic patient.